A 12-month-old American Indian boy presented to the emergency department (ED) of a rural hospital in eastern Arizona in cardiopulmonary arrest after being found unresponsive in his crib at home.
He was a previously healthy, fully immunized infant with no chronic medical conditions. He had attended all his scheduled well-child visits, and his growth and development were appropriate for his age. He had no prior documented cardiac or pulmonary history, and all prior examinations were normal, including documented absence of cardiac murmurs or extra beats. Medical history was notable for abscess of the thigh at age 6 months that was culture positive for methicillin-resistant Staphylococcus aureus and was successfully treated as an outpatient with incision, drainage and antibiotics. He was admitted to the hospital at 10 months of age for bronchiolitis after presenting with hypoxia, fever and chest radiograph showing hyperinflation, but without focal infiltrate. He had an uneventful recovery after being treated with ceftriaxone for 48 hours before discharge with amoxicillin/clavulanate and supplemental oxygen, which he required for < 7 days. There was no recent travel and no significant cardiopulmonary history in any first- or second-degree family members.
Recent events were notable for an ED visit when he presented with a fever (38 °C), cough and “right ear tugging.” He was diagnosed with acute otitis media and treated with azithromycin. The patient returned to his baseline and was in his usual state of health until 5 weeks later, when his condition deteriorated rapidly. That morning the boy woke up behaving normally and attended a parade with his family. In the early afternoon, he started moaning, became increasingly fussy and was given 1 dose of ibuprofen for comfort. He otherwise had no symptoms at that time; family denied ear tugging, runny nose or cough. Over the following 2 hours, he vomited once (nonbloody, nonbilious), had 2 loose yellow stools and was refusing liquids. The boy collapsed in his bed and was believed to have fallen asleep from exhaustion. Thirty minutes later, he was unresponsive and stiff. Emergency medical services were activated and the boy was found to be in asystole upon their arrival. Cardiopulmonary resuscitation was initiated in the field. The patient was successfully intubated on arrival to the ED. He received 8 rounds of intravenous epinephrine in addition dextrose, while cardiopulmonary resuscitation was resumed for an additional 30 minutes before he was declared deceased. There was no additional laboratory or radiologic workup performed during the resuscitation. An autopsy was performed, which ultimately revealed the diagnosis.
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Autopsy attributed his death to “acute and ongoing fulminant rheumatic carditis with … sections of the left ventricle and interventricular septum showing acute and ongoing rheumatic carditis with patchy areas of confluent Aschoff nodules throughout (Fig. 1), areas of resolving injury and fibrosis, and foci of granulation tissue.” Given the unexpected findings, the cardiac histology was reviewed by 3 pathologists including a specialist in myocardial histopathology who confirmed the diagnosis and additionally noted the globular nature of the heart.
This fatal case of fulminant rheumatic carditis in a 12-month-old Native American boy is the youngest such case reported in the past 50 years. A case series of 10 children under 3 years of age with acute rheumatic fever at a Boston hospital from 1939 to 1966 included a 19 months old,1 and a case report from Alabama described a fatal episode of rheumatic carditis in a 9 months old in 1963.2 These are the previously reported youngest ARF cases in the United States.
Streptococcus pyogenes (group A Streptococcus [GAS]) infections and post-GAS sequelae have persistent, deleterious and under-appreciated effects on indigenous populations, including American Indians/Alaska Natives (AIs/ANs). Guidelines recommend against testing children < 3 years of age for GAS pharyngitis, the preceding infection most commonly associated with acute rheumatic fever (ARF). While guidelines suggest testing may be considered in “selected” children < 3 years old with exposure to a sibling diagnosed with GAS infection or to infected parents or other household members, consideration of increased risk in indigenous communities is not addressed.3
These guidelines are premised on the notion that GAS infections and postinfectious sequelae are exceedingly rare in the very young. Yet, a meta-analysis showed the pooled prevalence of GAS pharyngitis in children < 5 years to be 24%.4 While the work by Shaikh et al4 suggests the risk of GAS pharyngitis is higher than previously assumed, available data are insufficient to predict the risk of ARF among both very young children and indigenous populations in the United States. Additionally, nonpharyngeal GAS infections are well described in this young age group. Streptococcal pyoderma (impetigo) has a median prevalence of 19% (interquartile range: 15%–31%) in children 0–4 years old,5 and among AI children on the Red Lake Reservation, 10% of impetigo occurred in children < 2 years of age.6 Invasive GAS has a bimodal distribution in the United States, with a peak incidence in children < 2 years,7 and disparately affects indigenous persons, as evidenced by a 13-year epidemiologic study that found rates of invasive GAS among AN children < 2 years of age more than 9 times higher compared with non-Native children (39.0 vs. 4.2 per 100,000).8 At best, there is inconsistent evidence to support the notion that GAS disease in young children (< 3 years) should be summarily dismissed.
There has been very little substantive research on postinfectious sequelae in AI/AN in recent decades. In the 1960s and 1970s, the rate of initial ARF attack on the Navajo reservation among the 5–24-year-old age group was 13.4–18.0 per 100,000.9 Although control programs led to a decrease in GAS throat colonization and the incidence of ARF, follow-up cost-benefit analysis suggested that future efforts should focus only on symptomatic children.10
A US-based study in the year 2000 found that children ≤ 5 years made up 20% of ARF hospitalizations, and notably, Asian/Pacific Islanders and AI/AN made up a greater proportion of ARF hospitalizations (6.3% and 1.2%, respectively) when compared with all-cause hospitalizations (2.0% and 0.5%, respectively), but this was not explored further.11 In the review by Sims Sanyahumbi et al12 on the global burden of GAS, they documented 18 studies on ARF in children since 2005, 8 of which took place in New Zealand or Australia, but none in the United States.
In Manitoba, Canada, the incidence of ARF in Native children under the age of 17 years was determined to be significantly higher when compared with non-Native children over a 10 years period: 126 versus 29 per 100,000.13 Similar findings were reported in northwestern Ontario, where the incidence rate of ARF among children of the First Nation’s communities was 75 times greater than Canada’s general population.14 These children lived in over-crowded dwellings and primary and secondary prevention efforts were thwarted by a lack of access to care and coordination of care.14 Similar circumstances exist for AI/AN.
Interestingly, growing evidence suggests that GAS impetigo, rather than GAS pharyngitis, is a major contributor to ARF among these indigenous children.15 Indigenous Australians, a community with the highest documented incidence of ARF globally, have low rates of GAS throat colonization, but 50%–70% of children are diagnosed with GAS pyoderma annually.16 In 2000, the incidence of GAS pharyngitis in 12 aboriginal communities was very low, but the annual incidence of ARF in children 5–14 years old was 508 per 100,000.17 Although, there are no comparable studies of AI/AN children in the United States in decades, recent data from our facility show rates of hospitalization for skin and soft tissue infection 9 times higher than the general population.18 Among 400 skin infections treated as an outpatient, > 50% were culture positive for GAS.19
Although speculative, our patient may have been suffering from macrolide-resistant GAS pharyngitis 5 weeks before his death when he presented with a febrile illness diagnosed as acute otitis media and was treated with azithromycin. No rapid test or culture for GAS was obtained. Rates of macrolide resistance in the United States vary by region, noted to be as high as 48%, but have increased over time, leading to the cautionary recommendation that macrolide antibiotics be reserved for GAS pharyngitis in patients with an anaphylactic-type penicillin allergy.20
Chart reviews of close contacts, parents, sibling and grandfather only yielded 2 significant infectious episodes, both in his mother. When the patient was 4 months old, his mother was diagnosed with streptococcal pharyngitis and treated with penicillin. Throat cultures were performed on close family contacts after his death and were all negative.
This case of fatal rheumatic carditis in a 12-month-old AI exposes the shortcomings of current guidelines. There are insufficient data on the current prevalence of GAS disease and subsequent ARF in AI/AN communities in the United States. This lack of data has led to the possible misapplication of guidelines on testing and treatment for GAS pharyngitis as well as missed opportunities to understand the contribution of GAS skin infections towards ARF. We encourage health authorities to invest in population-based surveillance of GAS disease among AI/AN children to better understand the links between pyoderma, pharyngitis and post-GAS sequelae.
The authors thank the patient’s family for allowing us to share their story in the hope that it will help inform the care of American Indians/Alaska Natives children.
1. Rosenthal A, Czoniczer G, Massell BF. Rheumatic fever under 3 years of age. A report of 10 cases. Pediatrics. 1968; 41:612–619.
2. Powell O, Miller RE. Rheumatic myocarditis in an infant nine months of age. J Pediatr. 1969; 74:123–125.
3. Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. 2012; 55:1279–1282.
4. Shaikh N, Leonard E, Martin JM. Prevalence of streptococcal pharyngitis and streptococcal carriage in children: a meta-analysis. Pediatrics. 2010; 126:e557–e564.
5. Bowen AC, Mahé A, Hay RJ, et al. The global epidemiology of impetigo: a systematic review of the population prevalence of impetigo and pyoderma. PLoS One. 2015; 10:e0136789.
6. Anthony BF, Kaplan EL, Wannamaker LW, et al. The dynamics of streptococcal infections in a defined population of children: serotypes associated with skin and respiratory infections. Am J Epidemiol. 1976; 104:652–666.
7. Nelson GE, Pondo T, Toews KA, et al. Epidemiology of invasive group A streptococcal infections in the United States, 2005-2012. Clin Infect Dis. 2016; 63:478–486.
8. Rudolph K, Bruce MG, Bruden D, et al. Epidemiology of invasive group A streptococcal disease in Alaska, 2001 to 2013. J Clin Microbiol. 2016; 54:134–141.
9. Coulehan J, Grant S, Reisinger K, et al. Acute rheumatic fever and rheumatic heart disease on the Navajo reservation, 1962-77. Public Health Rep. 1980; 95:62–68.
10. Coulehan JL, Baacke G, Welty TK, et al. Cost-benefit of a streptococcal surveillance program among Navajo Indians. Public Health Rep. 1982; 97:73–77.
11. Miyake CY, Gauvreau K, Tani LY, et al. Characteristics of children discharged from hospitals in the United States in 2000 with the diagnosis of acute rheumatic fever. Pediatrics. 2007; 120:503–508.
12. Sims Sanyahumbi A, Colquhoun S, Wyber R, et al. Ferretti JJ, Stevens DL, Fischetti VA. Global disease burden of group A streptococcus. In: Streptococcus Pyogenes: Basic Biology to Clinical Manifestations. 2016, University of Oklahoma Health Sciences Center; 661–704.
13. Longstaffe S, Postl B, Kao H, et al. Rheumatic fever in native children in Manitoba. Can Med Assoc J. 1982; 127:497–498.
14. Gordon J, Kirlew M, Schreiber Y, et al. Acute rheumatic fever in First Nations communities in northwestern Ontario: social determinants of health “bite the heart.” Can Fam Physician. 2015; 61:881–886.
15. Steer AC, Carapetis JR. Acute rheumatic fever and rheumatic heart disease in indigenous populations. Pediatr Clin North Am. 2009; 56:1401–1419.
16. McDonald M, Currie BJ, Carapetis JR. Acute rheumatic fever: a chink in the chain that links the heart to the throat? Lancet Infect Dis. 2004; 4:240–245.
17. Parnaby MG, Carapetis JR. Rheumatic fever in indigenous Australian children. J Paediatr Child Health. 2010; 46:527–533.
18. Davidson AM, Burgess T, Saguros A, et al. High rates of hospitalization due to skin and soft-tissue infections in a Southwest American Indian Population (#451). Paper presented at: IDWeek 2019, Washington, DC.
19. Galdun PD, Close RM, Sutcliffe C, et al. 444. Better efficiency, same accuracy: point-of-care PCR for the detection of group A streptococcus in noninvasive skin infections. Paper presented at: IDWeek 2019, Washington, DC.
20. Logan LK, McAuley JB, Shulman ST. Macrolide treatment failure in streptococcal pharyngitis resulting in acute rheumatic fever. Pediatrics. 2012; 129:e798–e802.